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  • Verbeek, JoostVU University Medical Center Amsterdam (author)

Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil.

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • Elsevier BV,2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-185287
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185287URI
  • https://doi.org/10.1016/j.nucmedbio.2011.10.017DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • OBJECTIVES: (R)-[(11)C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood-brain barrier in man. A disadvantage of (R)-[(11)C]verapamil is the fact that its main metabolite, [(11)C]D617, also enters the brain. For quantitative analysis of (R)-[(11)C]verapamil data, it has been assumed that the cerebral kinetics of (R)-[(11)C]verapamil and [(11)C]D617 are the same. The aim of the present study was to investigate whether the cerebral kinetics of (R)-[(11)C]verapamil and [(11)C]D617 are indeed similar and, if so, whether [(11)C]D617 itself could serve as an alternative PET tracer for P-gp.METHODS: [(11)C]D617 was synthesized and its ex vivo biodistribution was investigated in male rats at four time points following intravenous administration of [(11)C]D617 (50 MBq) without (n=4) or with (n=4) pretreatment with the P-gp inhibitor tariquidar (15 mg·kg(-1), intraperitoneally). Brain distribution was further assessed using consecutive PET scans (n=8) before and after pretreatment with tariquidar (15 mg·kg(-1), intravenously), as well as metabolite analysis (n=4).RESULTS: The precursor for the radiosynthesis of [(11)C]D617, 5-amino-2-(3,4-dimethoxy-phenyl)-2-isopropyl-pentanitrile (desmethyl D617), was synthesized in 41% overall yield. [(11)C]D617 was synthesized in 58%-77% decay-corrected yield with a radiochemical purity of ≥99%. The homogeneously distributed cerebral volume of distribution (V(T)) of [(11)C]D617 was 1.1, and this increased 2.4-fold after tariquidar pretreatment.CONCLUSION: V(T) of [(11)C]D617 was comparable to that of (R)-[(11)C]verapamil, but its increase after tariquidar pretreatment was substantially lower. Hence, (R)-[(11)C]verapamil and [(11)C]D617 do not show similar brain kinetics after inhibition of P-gp with tariquidar.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Syvänen, StinaLeiden University(Swepub:uu)stsyv838 (author)
  • Schuit, Robert C (author)
  • Eriksson, JonasVU University Medical Center Amsterdam(Swepub:uu)joeri542 (author)
  • de Lange, Elizabeth C (author)
  • Windhorst, Albert D (author)
  • Luurtsema, Gert (author)
  • Lammertsma, Adriaan A (author)
  • VU University Medical Center AmsterdamLeiden University (creator_code:org_t)

Related titles

  • In:Nuclear Medicine and Biology: Elsevier BV39:4, s. 530-90969-80511872-9614

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